Flash Radiotherapy Is Faster Than a Heartbeat: A Model to Illustrate the Interplay between Tissue Oxygen Perfusion and Ultra-High Dose Rate Effects.
Abstract
Purpose
To investigate ultra-high dose rate therapy (UHDRT) improves the protection of normal tissues and reduces side effects while effectively controlling tumors. Several hypotheses have been proposed to explain how ultra-high dose rates can produce these effects under various conditions. UHDRT involves brief exposure to radiation, which results in fewer heartbeats and reduced tissue oxygen perfusion during irradiation. However, the impact of tissue oxygen perfusion during UHDRT irradiation remains unclear.
Methods
We developed a compartmental model to simulate oxygen transfer and its interaction with radiation. The proposed model consists of three compartments: 1) the heart and arteries; 2) the irradiated brain's blood vessels and capillaries; and 3) the irradiated brain tissue. We employed a system of differential equations, incorporating experimental data from in vivo oxygen measurements using an Oxyphor probe in the brain, to determine the model's parameters.
Results
This model demonstrates how dose rate and oxygen perfusion could influence processes such as lipid peroxidation, potentially leading to differential biological effects. Our analysis of lipid peroxidation as a function of dose rate revealed a sigmoidal dose-rate-response curve that correlates well with published biological data. The results indicate that the differential effects of UHDR compared to conventional dose rates depend on factors such as oxygen perfusion, consumption, and tissue oxygen tension.
Conclusion
This suggests that the temporal dynamics of oxygen could play a crucial role in enhancing the therapeutic window for UHDR treatments. Furthermore, the magnitude of the observed effects due to UHDR may vary across different tissues or tumors and between experimental models (e.g., in vitro versus in vivo) based on these dynamics.